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Benralizumab maintains effectiveness in severe asthma at 2 years
out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.
Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.
In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.
Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.
The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta2-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.
The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.
The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.
A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.
A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.
The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).
Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.
AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.
SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.
out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.
Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.
In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.
Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.
The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta2-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.
The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.
The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.
A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.
A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.
The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).
Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.
AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.
SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.
out to 2 years, according findings of the BORA trial, an extension study of the phase 3 SIROCCO and CALIMA trials. The study follows up and reinforces previously reported 1-year data and was reported by William W. Busse, MD, of University of Wisconsin, Madison, and his colleagues in the Lancet Respiratory Medicine.
Benralizumab is a monoclonal antibody that targets interleukin-5 receptor alpha. It causes rapid deletion of eosinophils through cell-mediated cytotoxicity. A 30-mg dose of benralizumab every 8 weeks is approved for severe asthma treatment in Canada, Europe, Japan, the United States, and other countries.
In the second year of treatment, there were no new adverse events associated with depleted eosinophils, and the frequency of opportunistic infections was similar to that observed in the first year.
Eosinophilic inflammation occurs in about half of asthma cases and is associated with greater severity.
The 48-week SIROCCO trial, the 56-week CALIMA trial, and the 28-week ZONDA trial tested the effect of benralizumab 30 mg given every 4 weeks or 8 weeks, combined with high-dosage inhaled steroids and long-acting beta2-agonists. The 8-week dose of the drug reduced annual exacerbations by 51%, compared with placebo in the SIROCCO trial and by 28% in the CALIMA trial. In the ZONDA trial, benralizumab reduced oral glucocorticoid use by 75%, compared with placebo, and by 25% from baseline.
The BORA extension trial included participants in the previous three trials. In the current report, researchers presented results from the analysis from BORA participants recruited from the SIROCCO and CALIMA trials. Data from participants from all three trials will be reported in the future.
The analysis included 1,576 patients who continued to receive benralizumab after being assigned to the treatment arm in SIROCCO or CALIMA, or who had received placebo were randomized to benralizumab on the 4-week (n = 783; 265 from placebo) or 8-week dose (n = 793; 281 from placebo) schedule.
A total of 166 patients, or about 10% in each group, discontinued treatment. The frequency of any serious adverse event (SAE) ranged between 10% and 11% in all groups. SAEs associated with infections ranged from 1% to 3%, indicating that there were no significant differences in SAE frequencies between those who were originally assigned to placebo and those who originally received benralizumab. That suggests no safety differences between receiving the drug for 1 year or 2 years.
A total of 1,046 subjects had blood eosinophil counts of 300 cells per mcL or greater at baseline; 72% of these patients had no asthma exacerbations during the BORA study. This was true for 74% of patients in the 8-week treatment arm.
The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm, compared with placebo (95% confidence interval, 0.42-0.56) and 0.46 in the 8-week arm (95% CI, 0.39-0.53). For patients who started out on placebo, the crude exacerbation rate during BORA was 0.53 in the 4-week group (95% CI, 0.43-0.65) and 0.57 in the 8-week group (95% CI, 0.47-0.68).
Patients who started on benralizumab had similar exacerbation frequencies during year 1 and year 2.
AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.
SOURCE: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: The antibody had similar safety, efficacy in year 2 as in year 1.
Major finding: The crude asthma exacerbation rate for patients who received benralizumab in SIROCCO or CALIMA was 0.48 in the 4-week arm and 0.46 in the 8-week arm; the crude exacerbation rate during BORA was 0.53 in the 4-week group and 0.57 in the 8-week group.
Study details: Extension of randomized, clinical trial (n = 1,576).
Disclosures: AstraZeneca and Kyowa Hakko Kirin funded the studies. The authors have received fees from AstraZeneca and other pharmaceutical companies, and some are employees of AstraZeneca.
Source: Busse WW et al. Lancet Respir Med. 2019 Jan 1;7(1):46-59.
New CHEST expert panel advice on cough diagnosis
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
FROM THE JOURNAL CHEST®
No matter the valve, protective device cuts post-TAVR stroke risk
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
SAN DIEGO – A retrospective study and combined meta-analysis of patients undergoing transcatheter aortic valve replacement (TAVR) confirms the protective effect of the Sentinel cerebral embolic protection (CEP) device, regardless of the valve type used, on periprocedural stroke and mortality.
“The only significant predictor for being stroke free was use of the protective device. If you look at different valve types, you have an effect with use of the protection device with each of them,” Julia Seeger, MD, said in an interview at the Transcatheter Cardiovascular Therapeutics annual meeting.The finding just reinforces a decision that the institution made several years ago, to uniformly use embolic protection in TAVR procedures. Asked if she was convinced by the latest data on the utility of the device, she replied “Yes, definitely.”
Use of the device adds only a couple of minutes to the procedure time, and there haven’t been any adverse events associated with it, and no additional imaging agent was required, said Dr. Seeger, an interventional cardiologist at the University of Ulm (Germany).
The studies included patients being treated with the Medtronic CoreValve/Evolut, the mechanically implantable Boston Scientific Lotus, and the balloon-expandable Edwards Sapien. Subanalyses for all three valve types showed strong trends for reduction of strokes and mortality. Sentinel is the only Food and Drug Administration–approved device for reduction of strokes during TAVR procedures.
The Sentinel and Clean-TAVI trials showed the efficacy of the Sentinel device in reducing the number and volume of periprocedural cerebral lesions, but there were insufficient randomized data to draw conclusions about its relative efficacy among valve types. Dr. Seeger’s team analyzed data from 984 consecutive TAVR patients. The Sentinel device was used in 548, and not used in 436 consecutive patients. Self-expandable valves were used significantly more often in patients who underwent the procedure with CEP (22% vs. 6.0%). In the study population, 590 balloon-expandable valves, 246 mechanically implantable valves, and 148 self-expandable valves were used.
In the 72 hours after the procedure, mortality or stroke was lower in the CEP group (1.5% versus 4.4%, P less than .01), as was disabling stroke (0.6% versus 3.2%, P less than .01). When results were analyzed by valve types, the researchers found a relative risk reduction for all stroke of 76% with the use of CEP with balloon-expandable devices, 68% with mechanically expandable devices, and 57% with self-expandable devices.
The researchers also conducted a patient-level meta-analysis, incorporating data on 1,306 subjects with symptomatic severe aortic stenosis, including 363 from the Sentinel trial (243 with CEP), 100 patients from the CLEAN-TAVI trial (1:1 randomization to CEP), and 843 patients from the Sentinel-Ulm study (423 with CEP).
They matched patients for valve type, Society of Thoracic Surgeons’ risk score, atrial fibrillation, diabetes, sex, coronary artery disease, and peripheral vascular disease. The all-procedural stroke rate was 5.4% in patients who did not receive CEP, and 1.9% in those who did, for a risk reduction of 65%. Similarly, 72-hour mortality stroke risk was reduced by 66% with the CEP device. It occurred in 6.0% of non-CEP patients, compared to 2.1% of the CEP patients.
The meeting was sponsored by the Cardiovascular Research Foundation.
REPORTING FROM TCT 2018
Hepatitis C debrief: Therapy has matured, access issues remain
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
In the GI Patient Center, AGA offers resources to help ensure patients are receiving the best possible care and living their best life.
REPORTING FROM THE LIVER MEETING 2018
RAS inhibitors improve outcomes in TAVR patients
After transcatheter aortic valve replacement (TAVR), treatment with a renin-angiotensin system (RAS) inhibitor at hospital discharge is associated with lower risk of mortality and heart failure–related readmission, according to an analysis of Medicare patients.
RAS inhibitors may reverse left ventricular remodeling and improve function, which could explain the association, noted lead investigator Taku Inohara, MD.
The researchers analyzed data from consecutive Medicare patients who underwent TAVR, drawn from the Society of Thoracic Surgeons/American College of Cardiology TVT Registry. They included 15,896 propensity-matched patients from 417 U.S. centers.
At 1 year, a RAS inhibitor prescription at discharge was linked to a statistically significant relative 18% reduction in all-cause mortality (12.5% vs. 14.9%) and a 16% drop in heart failure readmissions (12.0% vs. 13.8%).
The researchers conducted a propensity-scored analysis of 12,942 patients with preserved left ventricular ejection fraction (greater than 40%) and 2,954 with LVEF up to 40%. In the preserved LVEF group, RAS inhibitor prescription was associated with a significant 22% reduction in mortality (11.1% vs. 13.9%), but there was no statistically significant association in patients with reduced LVEF (18.8% vs. 19.5%).
There was no clinically meaningful difference in quality of life between those who received a RAS inhibitor and those who did not, but the subgroup analysis could be performed on only 30% of the overall cohort, Dr. Inohara and his colleagues at the Duke Clinical Research Center in Durham, N.C., wrote.
They added that most patients undergoing TAVR are eligible for RAS inhibitors because of frequently comorbid hypertension, coronary artery disease, and renal dysfunction.
The study was funded by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the Society of Thoracic Surgeons. Study authors have wide-ranging financial relationships with pharmaceutical companies.
SOURCE: Inohara T et al. JAMA. 2018 Dec 4;320(21):2231-41.
After transcatheter aortic valve replacement (TAVR), treatment with a renin-angiotensin system (RAS) inhibitor at hospital discharge is associated with lower risk of mortality and heart failure–related readmission, according to an analysis of Medicare patients.
RAS inhibitors may reverse left ventricular remodeling and improve function, which could explain the association, noted lead investigator Taku Inohara, MD.
The researchers analyzed data from consecutive Medicare patients who underwent TAVR, drawn from the Society of Thoracic Surgeons/American College of Cardiology TVT Registry. They included 15,896 propensity-matched patients from 417 U.S. centers.
At 1 year, a RAS inhibitor prescription at discharge was linked to a statistically significant relative 18% reduction in all-cause mortality (12.5% vs. 14.9%) and a 16% drop in heart failure readmissions (12.0% vs. 13.8%).
The researchers conducted a propensity-scored analysis of 12,942 patients with preserved left ventricular ejection fraction (greater than 40%) and 2,954 with LVEF up to 40%. In the preserved LVEF group, RAS inhibitor prescription was associated with a significant 22% reduction in mortality (11.1% vs. 13.9%), but there was no statistically significant association in patients with reduced LVEF (18.8% vs. 19.5%).
There was no clinically meaningful difference in quality of life between those who received a RAS inhibitor and those who did not, but the subgroup analysis could be performed on only 30% of the overall cohort, Dr. Inohara and his colleagues at the Duke Clinical Research Center in Durham, N.C., wrote.
They added that most patients undergoing TAVR are eligible for RAS inhibitors because of frequently comorbid hypertension, coronary artery disease, and renal dysfunction.
The study was funded by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the Society of Thoracic Surgeons. Study authors have wide-ranging financial relationships with pharmaceutical companies.
SOURCE: Inohara T et al. JAMA. 2018 Dec 4;320(21):2231-41.
After transcatheter aortic valve replacement (TAVR), treatment with a renin-angiotensin system (RAS) inhibitor at hospital discharge is associated with lower risk of mortality and heart failure–related readmission, according to an analysis of Medicare patients.
RAS inhibitors may reverse left ventricular remodeling and improve function, which could explain the association, noted lead investigator Taku Inohara, MD.
The researchers analyzed data from consecutive Medicare patients who underwent TAVR, drawn from the Society of Thoracic Surgeons/American College of Cardiology TVT Registry. They included 15,896 propensity-matched patients from 417 U.S. centers.
At 1 year, a RAS inhibitor prescription at discharge was linked to a statistically significant relative 18% reduction in all-cause mortality (12.5% vs. 14.9%) and a 16% drop in heart failure readmissions (12.0% vs. 13.8%).
The researchers conducted a propensity-scored analysis of 12,942 patients with preserved left ventricular ejection fraction (greater than 40%) and 2,954 with LVEF up to 40%. In the preserved LVEF group, RAS inhibitor prescription was associated with a significant 22% reduction in mortality (11.1% vs. 13.9%), but there was no statistically significant association in patients with reduced LVEF (18.8% vs. 19.5%).
There was no clinically meaningful difference in quality of life between those who received a RAS inhibitor and those who did not, but the subgroup analysis could be performed on only 30% of the overall cohort, Dr. Inohara and his colleagues at the Duke Clinical Research Center in Durham, N.C., wrote.
They added that most patients undergoing TAVR are eligible for RAS inhibitors because of frequently comorbid hypertension, coronary artery disease, and renal dysfunction.
The study was funded by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the Society of Thoracic Surgeons. Study authors have wide-ranging financial relationships with pharmaceutical companies.
SOURCE: Inohara T et al. JAMA. 2018 Dec 4;320(21):2231-41.
REPORTING FROM JAMA
Key clinical point:
Major finding: Treatment was linked to reductions in 1-year mortality and heart failure of 18% and 16%, respectively.
Study details: Propensity matched, retrospective analysis of 15,896 Medicare patients.
Disclosures: The study was funded by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and the Society of Thoracic Surgeons. Study authors have wide-ranging financial relationships with pharmaceutical companies.
Source: Inohara T et al. JAMA. 2018 Dec 4;320(21):2231-41.
Hepatitis C debrief: Therapy has matured, access issues remain
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
REPORTING FROM THE LIVER MEETING 2018
Skin rashes often accompany drug-induced liver injury
SAN FRANCISCO – More than a quarter of drug-induced liver injury (DILI) cases also involve skin reactions, most often drug rash with eosinophilia and system symptoms (DRESS) syndrome. These dual cases of DILI and drug-induced skin injury (DISI) underscore the need for hepatologists to pay attention to dermatologic conditions and emphasize the need for the two specialties to work together.
The findings suggest that DISI/DILI comorbidity is not uncommon, and may hint at underlying mechanisms that could be used to tailor treatment, according to Harshad Devarbhavi, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. “My message was that people should work more and see if there’s any type of genotype or HLA [human leukocyte antigen] that produces this reaction. It’s a multisystem disease. It doesn’t belong to dermatologists, it’s a domain that also belongs to hepatologists,” said Dr. Devarbhavi, who is a hepatology fellow at St. John’s Medical College in Bangalore, India.
DISI is more common than DILI, and may or may not be caused by an immune response. The two conditions were previously known to co-occur, but it is rarely reported because dermatologists and hepatologists report findings in different journals.
The researchers defined DILI as a fivefold or greater increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT); a threefold or greater increase with symptoms, including cutaneous reactions; any elevation of AST, ALT, or alkaline phosphatase (ALP) accompanying a bilirubin increase of 2 mg/dL or more; or a twofold or higher increase in ALP combined with a cutaneous reaction.
They analyzed 921 DILI patients from a single registry in India, who were seen between 1997 and April 2018. All patients with skin reactions were seen by dermatologists and competing causes were excluded. A total of 28% of patients with DILI also had DISI, 13% of whom were also HIV positive; 56% developed jaundice. The mean age of patients with DILI/DISI was 35 years, compared with 42 years in DILI only patients (P = .001) and the mean duration of drug therapy was 42 days, compared with 89 days (P = .002). Twelve percent of DILI/DISI patients died, which was lower than the 17% mortality in those with DILI alone.
Of the DILI/DISI patients, 59% experienced DRESS, and 19% had Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Six percent of patients with DRESS died, as did 22% of those with SJS/TEN. Mortality was 16% among those with other skin manifestations. Eighteen percent of those with jaundice died, compared with 3% of those without jaundice.
Thirty patients with DILI/DISI died; 37% (11) of them had SJS/TEN, compared with 17% of survivors (P = .01). DRESS was more common in survivors (62% vs. 33%; P = .02).
Of DILI/DISI and SJS/TEN cases, 75% were associated with four drug classes: antiepileptic drugs, dapsone, antiretroviral therapies, and leflunomide.
“The liver is the biggest internal organ in the body, and skin is the largest external organ, so there is some correlation between the two, but people haven’t looked at it. People should come together and see why some drugs produce both these injuries. I think there is some mechanistic information in these drugs,” said Dr. Devarbhavi.
Source: Hepatology 2018 Oct 1;68[S1], Abstract 37.
SAN FRANCISCO – More than a quarter of drug-induced liver injury (DILI) cases also involve skin reactions, most often drug rash with eosinophilia and system symptoms (DRESS) syndrome. These dual cases of DILI and drug-induced skin injury (DISI) underscore the need for hepatologists to pay attention to dermatologic conditions and emphasize the need for the two specialties to work together.
The findings suggest that DISI/DILI comorbidity is not uncommon, and may hint at underlying mechanisms that could be used to tailor treatment, according to Harshad Devarbhavi, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. “My message was that people should work more and see if there’s any type of genotype or HLA [human leukocyte antigen] that produces this reaction. It’s a multisystem disease. It doesn’t belong to dermatologists, it’s a domain that also belongs to hepatologists,” said Dr. Devarbhavi, who is a hepatology fellow at St. John’s Medical College in Bangalore, India.
DISI is more common than DILI, and may or may not be caused by an immune response. The two conditions were previously known to co-occur, but it is rarely reported because dermatologists and hepatologists report findings in different journals.
The researchers defined DILI as a fivefold or greater increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT); a threefold or greater increase with symptoms, including cutaneous reactions; any elevation of AST, ALT, or alkaline phosphatase (ALP) accompanying a bilirubin increase of 2 mg/dL or more; or a twofold or higher increase in ALP combined with a cutaneous reaction.
They analyzed 921 DILI patients from a single registry in India, who were seen between 1997 and April 2018. All patients with skin reactions were seen by dermatologists and competing causes were excluded. A total of 28% of patients with DILI also had DISI, 13% of whom were also HIV positive; 56% developed jaundice. The mean age of patients with DILI/DISI was 35 years, compared with 42 years in DILI only patients (P = .001) and the mean duration of drug therapy was 42 days, compared with 89 days (P = .002). Twelve percent of DILI/DISI patients died, which was lower than the 17% mortality in those with DILI alone.
Of the DILI/DISI patients, 59% experienced DRESS, and 19% had Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Six percent of patients with DRESS died, as did 22% of those with SJS/TEN. Mortality was 16% among those with other skin manifestations. Eighteen percent of those with jaundice died, compared with 3% of those without jaundice.
Thirty patients with DILI/DISI died; 37% (11) of them had SJS/TEN, compared with 17% of survivors (P = .01). DRESS was more common in survivors (62% vs. 33%; P = .02).
Of DILI/DISI and SJS/TEN cases, 75% were associated with four drug classes: antiepileptic drugs, dapsone, antiretroviral therapies, and leflunomide.
“The liver is the biggest internal organ in the body, and skin is the largest external organ, so there is some correlation between the two, but people haven’t looked at it. People should come together and see why some drugs produce both these injuries. I think there is some mechanistic information in these drugs,” said Dr. Devarbhavi.
Source: Hepatology 2018 Oct 1;68[S1], Abstract 37.
SAN FRANCISCO – More than a quarter of drug-induced liver injury (DILI) cases also involve skin reactions, most often drug rash with eosinophilia and system symptoms (DRESS) syndrome. These dual cases of DILI and drug-induced skin injury (DISI) underscore the need for hepatologists to pay attention to dermatologic conditions and emphasize the need for the two specialties to work together.
The findings suggest that DISI/DILI comorbidity is not uncommon, and may hint at underlying mechanisms that could be used to tailor treatment, according to Harshad Devarbhavi, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Diseases. “My message was that people should work more and see if there’s any type of genotype or HLA [human leukocyte antigen] that produces this reaction. It’s a multisystem disease. It doesn’t belong to dermatologists, it’s a domain that also belongs to hepatologists,” said Dr. Devarbhavi, who is a hepatology fellow at St. John’s Medical College in Bangalore, India.
DISI is more common than DILI, and may or may not be caused by an immune response. The two conditions were previously known to co-occur, but it is rarely reported because dermatologists and hepatologists report findings in different journals.
The researchers defined DILI as a fivefold or greater increase in aspartate aminotransferase (AST) or alanine aminotransferase (ALT); a threefold or greater increase with symptoms, including cutaneous reactions; any elevation of AST, ALT, or alkaline phosphatase (ALP) accompanying a bilirubin increase of 2 mg/dL or more; or a twofold or higher increase in ALP combined with a cutaneous reaction.
They analyzed 921 DILI patients from a single registry in India, who were seen between 1997 and April 2018. All patients with skin reactions were seen by dermatologists and competing causes were excluded. A total of 28% of patients with DILI also had DISI, 13% of whom were also HIV positive; 56% developed jaundice. The mean age of patients with DILI/DISI was 35 years, compared with 42 years in DILI only patients (P = .001) and the mean duration of drug therapy was 42 days, compared with 89 days (P = .002). Twelve percent of DILI/DISI patients died, which was lower than the 17% mortality in those with DILI alone.
Of the DILI/DISI patients, 59% experienced DRESS, and 19% had Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Six percent of patients with DRESS died, as did 22% of those with SJS/TEN. Mortality was 16% among those with other skin manifestations. Eighteen percent of those with jaundice died, compared with 3% of those without jaundice.
Thirty patients with DILI/DISI died; 37% (11) of them had SJS/TEN, compared with 17% of survivors (P = .01). DRESS was more common in survivors (62% vs. 33%; P = .02).
Of DILI/DISI and SJS/TEN cases, 75% were associated with four drug classes: antiepileptic drugs, dapsone, antiretroviral therapies, and leflunomide.
“The liver is the biggest internal organ in the body, and skin is the largest external organ, so there is some correlation between the two, but people haven’t looked at it. People should come together and see why some drugs produce both these injuries. I think there is some mechanistic information in these drugs,” said Dr. Devarbhavi.
Source: Hepatology 2018 Oct 1;68[S1], Abstract 37.
REPORTING FROM THE LIVER MEETING 2018
Key clinical point: Researchers hope the findings will shed light on the mechanism of injury.
Major finding: 28% of patients with DILI also had a skin rash.
Study details: Retrospective analysis of 921 DILI patients.
Disclosures: No source of funding was disclosed. Dr. Devarbhavi disclosed no relevant conflicts.
Source: Hepatology 2018 Oct 1;68[S1], Abstract 37.
The Liver Meeting 2018: Hepatitis B novel therapies debrief – key abstracts
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
REPORTING FROM THE LIVER MEETING 2018
Hep C–infected livers are safe for transplant
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
REPORTING FROM THE LIVER MEETING 2018
Key clinical point: Use of hepatitis C–positive livers can significantly increase the donor organ pool.
Major finding: Hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality.
Study details: Retrospective analysis of 16,858 liver transplants.
Disclosures: The study was funded internally. Dr. Paul has no financial disclosures.
Source: AASLD 2018, Abstract 0249.
Prolonged DAPT doesn’t help left main CAD
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
SAN DIEGO – Among patients who receive a drug-eluting stent (DES) in their left main coronary artery (LMCA), continuation of dual antiplatelet therapy (DAPT) past 1 year appears to provide no benefit.
The results come from a subanalysis of the EXCEL trial, which compared the Xience DES to coronary artery bypass graft (CABG) surgery in LMCA lesions.
The LMCA is worrisome to a lot of physicians because of the large amount of myocardial tissue it contains, and they often prescribe DAPT past the generally recommended 1 year. “It’s this magic thing, that ‘Well, it’s left main stenting, and you’d better protect the patient.’ But it turns out that it doesn’t,” said Sorin Brener, MD, director of the catheterization lab at New York Methodist Hospital, who presented the results of the study at the Transcatheter Cardiovascular Therapeutics annual meeting.
The researchers compared patients in both groups who opted to stop DAPT after 1 year versus those who continued therapy out to 3 years, and the news was not favorable for continuation. A composite of death, myocardial infarction, or stroke was higher among patients who continued DAPT, though the results did not reach statistical significance.
It’s possible that patients who continued DAPT were more ill on average. “Obviously, there could be cases where the doctor decided they deserved more prolonged therapy, but it’s not measurable, so I don’t think they were sicker,” said Dr. Brener.
The study was also underpowered. Those worse trends probably don’t represent a real signal, according to Dr. Brener. Rather, they suggest that there is no significant difference between the approaches. “The signal just tells you that there is no difference, and that prolonging DAPT probably just induces some minor bleeding, but it doesn’t protect you. So the message would be that you should treat all your patients the same way regardless of where you put the stent,” said Dr. Brener.
The researchers compared data from 497 patients in the EXCEL trial who continued DAPT out to 3 years with that from 136 who stopped DAPT early (115 stopped in year 1-2; 21 stopped in year 2-3). The baseline characteristics of the two groups were similar except for a higher incidence of recent MI in the group that stopped DAPT early (21.3% vs. 13.7%; P = .03).
At 3 years, death, MI, or stroke occurred in 7.8% of the continuation group and in 5.2% of the patients who stopped DAPT. All-cause mortality was 5.8% in the continuation group compared with 2.3% of those who stopped. When the researchers restricted the analysis to patients who presented with acute coronary syndrome, 7.6% and 3.6%, respectively, met the primary endpoint. None of these differences reached statistical significance.
The study was limited by a high dropout rate from DAPT in the first year: 152 patients stopped taking the medication even though they experienced no events, and they were excluded from the analysis.
The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
SOURCE: Brener S. TCT 2018, Abstract TCT-1.
REPORTING FROM TCT 2018
Key clinical point: Prolonged DAPT was not associated with better outcomes.
Major finding: Composite death, myocardial infarction, and stroke was similar between the two groups.
Study details: A post hoc analysis of 633 patients in the EXCEL trial.
Disclosures: The EXCEL trial was funded by Abbott. Dr. Brener has been a consultant or received honoraria or speaker’s fees for AstraZeneca.
Source: Brener S. TCT 2018, Abstract TCT-1.